Biochemical and Biophysical Research Communications 1999-01-19

Interaction of novel thiocolchicine analogs with the tubulin isoforms from bovine brain.

A Banerjee, L T Kasmala, E Hamel, L Sun, K H Lee

Index: Biochem. Biophys. Res. Commun. 254(2) , 334-7, (1999)

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Abstract

The antimitotic alkaloid colchicine binds to tubulin and inhibits microtubule assembly. Recently a new series of colchicine derivatives has been synthesized in which the seven-membered B-ring was shortened to a six-membered ring. In an effort to study the role of the B-ring substituents in this new series, we have studied the interaction of two compounds of this series, THC 5 and THC 18, with tubulin isoforms from bovine brain. We find that THC 18, which has a side chain with a pi-bonded SP2 conformation, binds differently to the tubulin isoforms, while THC 5 with a slightly different side chain does not. The results indicate that the conformation of the B-ring domain plays a major role in the differential interaction of a colchicine derivative with different tubulin isoforms. The results will be very important in designing potent antitumor derivatives of colchicine.Copyright 1999 Academic Press.